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用于可注射药物释放凝胶的基于热敏叶酸的超分子杂化凝胶的制备

Fabrication of thermal sensitive folic acid based supramolecular hybrid gels for injectable drug release gels.

作者信息

Song Yahui, Gao Jianping, Xu Xiaoyang, Zhao Huilin, Xue Ruinan, Zhou Jingkuo, Hong Wei, Qiu Haixia

机构信息

School of Science, Tianjin University, Tianjin 300072, China.

School of Science, Tianjin University, Tianjin 300072, China.

出版信息

Mater Sci Eng C Mater Biol Appl. 2017 Jun 1;75:706-713. doi: 10.1016/j.msec.2017.02.118. Epub 2017 Feb 24.

DOI:10.1016/j.msec.2017.02.118
PMID:28415519
Abstract

Thermal sensitive supramolecular hybrid gels for injectable drug release were prepared by adding different amounts of agar into folic acid (FA) gelator. The gelation temperature was modulated in order to form injectable gel with body temperature (37°C). Such kind of folic acid-agar (FAG) hybrid gel makes it possible to use supramolecular gel as injectable drug loaded gels for drug release. FT-IR and UV-vis spectra indicate that agar macromolecules involve in the self-assembly process through intermolecular H-bonding and π-π stacking interactions with FA molecules. The SEM and TEM images demonstrate that the fiber diameter of FAG hybrid gel is about 20nm, much smaller than that of FA gel (40nm). However, FAG hybrid has a denser nano-fibrous network structure than FA gels. Moreover, FAG hybrid gel is endowed with a more ordered network structure and a little better crystallization capability by adding agar. FAG hybrid gel also shows a shear-thinning behavior but the shear viscosity is about 2 times higher than that of FA gel. Compared with FA gel, the storage (G') and loss (G″) moduli of the FAG gel are higher, which implies an enhanced gel strength. At the same time, both FA and FAG gels are facilely affected by some external factors such as acid, base and salts. In acidic or basic conditions, the strength became weak and the gelation temperature (Tg) decreased. While, within certain concentrations, the salt (NaCl) increased the gel strength and Tg. FAG gel suffered lower mass loss and owned better stability in different pH solutions compared with pure FA gel. The release behavior of the FA and injectable FAG gels was investigated by using Rhodamine B as a mimic model drug. FAG hybrid gel shows a long release profile and the release time is 3 times longer than that of FA gel, up to 30h, and the accumulative release amount reaches about 86%. So it is a potential injectable gel for sustained release drug delivery system.

摘要

通过向叶酸(FA)凝胶剂中加入不同量的琼脂,制备了用于可注射药物释放的热敏超分子混合凝胶。调节凝胶化温度以形成体温(37°C)下的可注射凝胶。这种叶酸 - 琼脂(FAG)混合凝胶使得超分子凝胶能够用作载药可注射凝胶用于药物释放。傅里叶变换红外光谱(FT - IR)和紫外可见光谱表明,琼脂大分子通过与FA分子的分子间氢键和π - π堆积相互作用参与自组装过程。扫描电子显微镜(SEM)和透射电子显微镜(TEM)图像表明,FAG混合凝胶的纤维直径约为20nm,远小于FA凝胶(40nm)。然而,FAG混合物具有比FA凝胶更致密的纳米纤维网络结构。此外,通过添加琼脂,FAG混合凝胶具有更有序的网络结构和稍好的结晶能力。FAG混合凝胶也表现出剪切变稀行为,但剪切粘度比FA凝胶高约2倍。与FA凝胶相比,FAG凝胶的储能模量(G')和损耗模量(G'')更高,这意味着凝胶强度增强。同时,FA和FAG凝胶都很容易受到一些外部因素如酸、碱和盐的影响。在酸性或碱性条件下,强度变弱且凝胶化温度(Tg)降低。而在一定浓度范围内,盐(NaCl)增加了凝胶强度和Tg。与纯FA凝胶相比,FAG凝胶在不同pH溶液中的质量损失更低且稳定性更好。以罗丹明B作为模拟模型药物研究了FA和可注射FAG凝胶的释放行为。FAG混合凝胶显示出长时间的释放曲线,释放时间比FA凝胶长3倍,长达30小时,累积释放量达到约86%。因此,它是一种用于缓释药物递送系统的潜在可注射凝胶。

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